The hippocampus is a crucial player across several learning and memory domains, and is highly vulnerable to alterations during aging. Several products of neurotransmitter genes and neuromodulator genes (which play important parts in mediating and maintaining cognitive ability as a function of age) are expressed in hippocampal formation. However, they represent only a small fraction of genes known to be expressed in this region. We review here recent studies on the use of cDNA microarray and proteomic approaches to uncover novel genes and pathways that might be involved in cognitive processes in the aged brain. We and other authors have demonstrated major individual differences in cognitive ability in rats of a similar age, thereby making it possible to directly compare gene products expressed as a function of age and cognitive status. Examples of the possible functional role of some of these genes (e.g. transthyretin, quinone reductase 2) and gene products are discussed.